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细胞色素P450花生四烯酸表氧化酶抑制LPS诱导的内皮细胞损伤的保护作用

发表时间:2014-06-15  浏览量:1753  下载量:754
全部作者: 刘婉君,曾和松
作者单位: 华中科技大学同济医学院附属同济医院心血管内科高血压研究所
摘 要: 目的:研究细胞色素P450(cytochrome P450,CYP)表氧化酶对脂多糖(lipopolysaccharides,LPS)诱导的血管内皮细胞(human umbilical vein endothelial cells,HUVECs)损伤以及炎症因子表达的变化及机制。方法:经转染表氧化酶基因 CYP2C8和直接加入环氧二十碳烯酸(epoxyeicosatrienoic acids,EETs)干预人脐静脉HUVECs,然后再以LPS干预,使用Western blotting分析细胞核NF-κB蛋白和细胞凋亡相关蛋白Bcl-2,Bax的表达情况,并通过流式细胞计数检测细胞凋亡情况。结果:转染CMV-CYP2C8质粒和直接加入EETs均明显抑制LPS所诱导的核因子NF-κB的激活而导致炎症因子IL-6,MCP-1的分泌,以及抗凋亡蛋白Bcl-2的减少、凋亡蛋白Bax的增多及细胞凋亡增多,并且使用过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor γ, PPARγ)抑制剂后,上述作用均被部分抑制。结论:细胞色素CYP2C8表氧化酶及代谢产物能明显抑制LPS诱导的HUVECs凋亡,可能通过抑制NF-κB的核转位发挥抗凋亡作用,PPARγ信号通路也可能参与该过程。
关 键 词: 心血管病学;花生四烯酸细胞色素表氧化酶P450;动脉粥样硬化;脂多糖;炎症;凋亡
Title: A potential therapeutic effect of arachidonic acid catalysed by cytochrome P450 epoxygenases on anti-LPS activity
Author: LIU Wanjun, ZENG Hesong
Organization: Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Abstract: Objective: To test mechanisms for that arachidonic acid catalysed by cytochrome P450 (CYP) epoxygenases resistance to the damage and expression of inflammatory cytokines induced by lipopolysaccharides (LPS) in human umbilical vein endothelial cells (HUVECs). Methods: In our study, we used CYP2C8 gene transfection and direct epoxyeicosatrienoic acids (EETs) intervention before LPS infused in HUVECs, then examined the expression of NF-κB and the apoptsis related protein Bcl-2, Bax by Western blotting and apoptosis by flow cytometry examination. Results: CMV-CYP2C8 transfection and direct intervention of EETs markedly suppressed LPS induced inflammatory cytokines IL-6 and MCP-1 expression via activation of NF-κB. In addition, the expression of anti-apoptosis proteins Bcl-2 decreased and the pro-apoptosis proteins Bax increased. Moreover, after using of peroxisome proliferator-activated receptor γ (PPARγ) inhibitors, these effects were partially inhibited. Conclusion: Our results demonstrated that CYP2C8-derived EETs had anti-vascular inflammatory and anti-apoptosis effects, at least in part, through activation of PPARγ.
Key words: cardiology; arachidonic acid cytochrome P450 epoxygenase; atherosclerosis; lipopolysaccharide; inflammation; apoptosis
发表期数: 2014年6月第11期
引用格式: 刘婉君,曾和松. 细胞色素P450花生四烯酸表氧化酶抑制LPS诱导的内皮细胞损伤的保护作用[J]. 中国科技论文在线精品论文,2014,7(11):1049-1054.
 
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